A new landmark study suggests that some patients with early-stage prostate cancer can be safely observed rather than undergoing radical surgery.

WATCHFUL WAITING (OBSERVATION) VERSUS SURGERY FOR PROSTATE CANCER

In the United States, prostate cancer is the most common type of non-skin cancer occurring among men, and the second most common cause of cancer death in men. (Lung cancer, an almost completely preventable form of cancer, sadly, remains the most common cause of cancer death for both men and women.) The American Cancer Society estimates that, in 2012, more than 240,000 new cases of prostate cancer will be diagnosed, and more than 28,000 men will die from this form of cancer.

The debate surrounding the ideal management of early-stage prostate cancer has revolved around “watchful waiting” (observation) versus aggressive treatment with surgery or radiation therapy. In many cases, prostate cancer is a slow-growing cancer, and when it arises in older men in particular, it seldom leads to death. On the other hand, there are more aggressive variants of prostate cancer that spread rapidly, and these forms of prostate cancer can indeed lead to death. The dilemma regarding which patients can be safely observed and which should be subjected to aggressive treatment has been difficult to resolve, however, because it can be difficult to determine, up front, which patients will benefit from treatment and which will not.

Last year, I reviewed a prospective randomized clinical research study from Sweden which revealed a significant improvement in survival among patients with prostate cancer who underwent prostate cancer surgery, when compared to patients who were managed with “watchful waiting” (Prostate Cancer: Watchful Waiting Versus Surgery (Prostatectomy).) Now, a similar new prospective randomized clinical research study provides additional important clinical information that may help doctors to identify selected prostate cancer patients who can be safely observed, thus avoiding radical cancer treatments that are associated with a high incidence of incontinence and impotence, as well as other potentially serious complications. This new study appears in the current issue of the New England Journal of Medicine, the same journal that published last year’s Swedish prostate cancer clinical research study.

In this prospective randomized study, 731 men with newly diagnosed prostate cancer were randomly assigned to undergo radical prostate cancer surgery (prostatectomy) versus observation only. This group of research volunteers, with an average age of 67 years, was then followed for approximately 10 years, and their outcomes were carefully monitored. It is important to note that all of these men had early-stage prostate cancer, which appeared not to have spread outside of the prostate gland.

Following 10 years of monitoring, on average, 47 percent of the men who underwent prostatectomy died, while 50 percent of the men in the observation group died (this small difference in overall survival was not statistically significant.) When the researchers looked at the risk of death caused specifically by prostate cancer, or due to complications associated with prostatectomy, 5.8 percent of the men in the prostatectomy group died directly as a result of either their prostate cancer or due to complications of surgery, while 8.4 percent of the men in the observation group died due to their prostate cancer, for a relative cancer-specific survival difference of 37 percent and an absolute difference of 2.6 percent in favor of the men who underwent surgery instead of observation. Importantly, however, this observed difference in cancer-specific survival did not quite achieve statistical significance, suggesting that the cancer-specific survival benefit of radical prostatectomy in men with early-stage prostate cancer is, in general, either nonexistent or very small, at least over a 10-year period of time.

Importantly, when the authors of this study assessed prostate-specific antigen (PSA) levels, specifically, as a predictor of survival among the two groups of men who participated in this study, they found that prostatectomy did, in fact, significantly improve survival among men with a PSA level greater than 10 nanograms per milliliter (ng/ml), compared to observation alone.

As is often the case, pundits on either side of the prostate cancer treatment debate will find some ammunition in this study’s findings to support their respective positions. Those experts who espouse aggressive treatment for most or all early-stage prostate cancers will note the nearly 3 percent improvement in absolute survival associated with radical prostatectomy, although, in this study, this difference in absolute survival was not considered to be statistically significant. (However, it should be noted that the observed survival advantage associated with surgery in this study would have actually been higher, and perhaps statistically significant as well, had there not been a postsurgical death of one of the patients in the prostatectomy group.) On the other hand, proponents of “watchful waiting” will point to the very small difference in observed death rates between these two groups of patients, and the relatively large number of adverse events associated with radical prostatectomy (21 percent). However, in my view, this study’s findings offer a reasonable, evidence-based, “middle ground” strategy, based upon patients’ PSA levels. Specifically, for older patients who have a PSA level below 10 ng/ml and no worrisome microscopic features that suggest an aggressive variant of prostate cancer, observation may indeed be a reasonable alternative to prostatectomy, based upon the findings of this landmark study. (Unfortunately, this study did not assess radiation therapy, which is the other common form of treatment for early-stage prostate cancer.)

In completing my review of this important clinical study, I should also note that 1 out of 5 patients who enrolled in this prospective study did not remain within their assigned groups and, therefore, crossed over into the opposite group after they entered into this study. However, while this factor does somewhat complicate the analysis of the data collected in this study, it probably does not affect the overall accuracy of the study’s conclusions.

I do not believe that this important but admittedly imperfect study will, by itself, completely resolve the ongoing debate regarding the optimal management of early-stage prostate cancer. However, as one of only a very few well-performed randomized prospective clinical studies that have directly compared radical surgery with observation alone, and with reasonable long-term follow-up of patients, this is a very important clinical research study for both patients and their prostate cancer physicians alike. Because of this study, both patients and their doctors will now be better able to make individualized, evidence-based decisions regarding the likely risks and benefits of surgery versus careful observation as an initial approach to prostate cancer management.

At this time, more than 8 percent of Americans are unemployed. According to the Bureau of Labor Statistics, however, the unemployment rate for veterans who served on active duty between September 2001 and December 2011 is now more than 12 percent. A new website, Veterans in Healthcare, seeks to connect veterans with potential employers. If you are a veteran who works in the healthcare field, or if you are an employer who is looking for physicians, advanced practice professionals, nurses, corpsmen/medics, or other healthcare professionals, then please take a look at Veterans in Healthcare. As a retired veteran of the U.S. Army, I urge you to hire a veteran whenever possible.

Disclaimer: As always, my advice to readers is to seek the advice of your physicianbeforemaking any significant changes in medications, diet, or level of physical activity

Dr. Wascher is an oncologic surgeon, professor of surgery, cancer researcher, oncology consultant, and a widely published author

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